43.2 Regulation of cell growth in tumours Flashcards
What are thought to be the 8 hallmarks of cancer?
- Self-sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Altered cellular metabolism
- Evasion of apoptosis
- Limitless replicative potential (immortality)
- Sustained angiogenesis
- Invasion and metastasis
- Evasion of immune surveillance
What is the true definition of cell growth compared to what it is often misled to be?
Cell growth = increase in cell size without division. Often incorrectly referred to as increase in size of a tissue/organ by cell division (this is division).
What are two key markers of malignant transformation?
- Self-sufficiency in growth signals, independent from normal growth factors
- Replicative immortality
What is the difference between hypertrophy and hyperplasia?
Hypertrophy - increase in size of an organ due to swelling of individual cells
Hyperplasia - increase in size of an organ due to an increased number of cells
How is cellular transformation different from normal cell growth?
In cellular transformation there is:
*independence from mitogens (growth factors)
*The potential for unlimited cell division (‘immortality’)
How do tumour cells gain replicative immortality?
Expression of TELOMERASE
How do tumour cells gain self-sufficiency in growth signals?
- Secrete their own growth factors
- Induce stromal cells to produce growth factors in the tumour microenvironment
Is cellular transformation enough to cause malignancy?
No
What are examples of other processes besides transformation must occur for a tumour to become malignant?
- Activation of tumour suppressor genes (otherwise - necrosis and apoptosis occurs)
- Neovascularisation - to supply increased demand as tumour grows
What are processes that limit tumour cell proliferation?
- Many cells in tumour are not actively proliferating
- Full cellular differentiation (cells cease proliferation)
- Cell death (necrosis/apoptosis)
- Cell loss (e.g. skin, gut, shedding into circulation)
What are the three different routes growth factors may arrive at the cell by?
Autocrine pathway - factor is produced by cell itself but acts on it to stimulate growth. ‘Room’ for similar cells.
Paracrine - factor is produced by a cell in close proximity, mediated by short-range molecules
Endocrine - factor is produced at some distance to affected cells and carried to it by blood, i.e. hormones.
What is malignant transformation?
The process by which cells acquire the properties of cancer
Why do normal (non-stem) cells have a limited number of cell cycles?
Telomeres shorten with each division - due to leading and lagging strands not being replicated symmetrically
Reach limit and cell becomes senescent
